The only way you can accomplish this is by using the ArcMap default scale in the layout, adding a text message beside it, identifying the layer referenced, then, with another text callout, type in the specific layer # 2 and the reference scale you wish to identify for it. With manual typing, you can add as many layer scale references as you wish to take the time for, for whatever reason you may want additional scale references. These additional scale references will, of course, be in a text scale format and will not have a graphic component.

If you set the default to A in = B mi, then the second could be x in = y ft. Just be sure that your typed scale calculation for each layer matches that set for the data frame overall.

I know of no other way to set multiple scale references in an ArcMap layout view. But I have trouble understanding why you would want to do so in the first place. It would seem to be confusing to your viewer.

Each layer can be controlled independently. In ArcMap, double-click on the layer to bring up its properties. Under the "General" tab is a place to set scale ranges. You can also group layers and then set scale ranges for groups of layers. To control symbol sizes at different scales, I have just added the layer twice to the map document and set different sized symbols visible within different scale ranges. You can do even more with the labels, because you can select the option to "Define different classes and label differently"--you can just define a "class" as a scale range and set the label properties appropriately for that scale range.